Intrinsic resistance to ROS1 inhibition in a patient with CD74-ROS1 mediated by AXL overexpression.

ABSTRACT:

Background

The vast majority of patients with ROS1 positive non-small cell lung cancer (NSCLC) derive clinical benefit from currently approved ROS1 therapies, including crizotinib and entrectinib. However, a small proportion of patients treated with ROS1 inhibitors fail to derive any clinical benefit and demonstrate rapid disease progression. The biological mechanisms underpinning intrinsic resistance remain poorly understood for oncogene-driven cancers.

Methods

We generated a patient-derived cell line, CUTO33, from a ROS1 therapy naive patient with CD74-ROS1+ NSCLC, who ultimately did not respond to a ROS1 inhibitor. We evaluated a panel of ROS1+ patient-derived NSCLC cell lines and used cell-based assays to determine the mechanism of intrinsic resistance to ROS1 therapy.

SUBMITTER: Peters TL 

PROVIDER: S-EPMC10665781 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature